LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma
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Cancer Cell International Open Access
PRIMARY RESEARCH
LncRNA ST7‑AS1, by regulating miR‑181b‑5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma Rong‑Hang Hu1, Zi‑Teng Zhang1, Hai‑Xiang Wei1, Lu Ning1, Jiang‑Shan Ai2, Wen‑Hui Li1, Heng Zhang3* and Shao‑Qiang Wang1*
Abstract Background: Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). Methods: The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. Results: ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accom‑ plished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. Conclusions: ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD. Keywords: ST7-AS1, Lung adenocarcinoma, Epithelial-mesenchymal transition, miR-181b-5p, KPNA4
*Correspondence: [email protected]; [email protected] 1 Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, No. 89, GuHuai Road, Jining 272029, Shandong, People’s Republic of China 3 Department of Thoracic Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, People’s Republic of China Full list of author information is available at the end of the article
Background Lung cancer remains the cancer with the highest mortality, non-small cell lung cancer (NSCLC) still accounts for approximately 85% of all new lung cancer cases [1, 2]. Lung adenocarcinoma (LUAD), a subtype of NSCLC, accounts for almost 50% of NSCLC, and the prognosis for patients with LUAD is generally poor [3]. Due to tumour metastasi
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